Pharmaceuticals have been conventionally administered, either in oral or parenteral dosage forms. However, these dosage forms are not always well suited for particular drugs or prolonged drug therapies. Many pharmaceuticals cannot be administered orally and patient noncompliance with dosage instructions is also a significant problem with oral dosage forms. To overcome these and other short comings of these dosage forms several new dosage forms have recently been developed.
The most notable recent development has been the use of bioerodible or bioabsorbable polymer matrices as carriers for implantable or intrauterine devices. Several publications describe these materials such as U.S. Pat. No. 4,304,767 to Heller et al., "Biodegradable block copolymer matrices for long-acting contraceptives with constant release" J. Contr. Rel. 32 (1992) 3-14 by Z. W. Gu et al., and U.S. Pat. No. 5,030,457 to Ng.
Heller describes a family bioabsorbable poly(ortho esters) which may be used as a matrix for controlled drug release. The polymers Heller et al. describes are synthesized by reacting a polyol with a diketene acetal. The polymers produced by this synthesis tend to be rigid because of the pentaerythritol segments in the polymer backbone. Unfortunately, this limits the use of these polymers to solid implants which generally must be surgically implanted.
Similarly, Gu et al. describes hard microspheres triblock copolymer of poly(e-caprolactone-co-DL-lactide-co-glycolide) for the controlled release of contraceptives. The microspheres that Gu et al., describes are designed to be injected thereby avoiding the need to surgically implant a solid dosage. Unfortunately, these copolymers must be formed into microspheres and the kinetics of the pharmaceutical release are complicated by the different release mechanisms of the individual blocks of the triblock copolymer.
Ng describes a bioerodible polymer poly(ortho ester) formed from a one step reaction of a ortho ester and a triol. These polymer are more flexible than the polymers described by Heller and can be employed in ointments, gels and creams. Unfortunately the poly(ortho esters) described by Ng are highly susceptible to acid hydrolysis which limits their utility as a carrier for acidic pharmaceuticals.
Thus it would be a significant contribution to the art to provide a bioabsorbable polymer that is easy to administer and slowly hydrolyses as it releases a drug.